tbuckley/cabot-search huggingface dataset:
Abstract 13265: Soluble Klotho Captures FGF23 to Mitigate Aortic Valve Inflammocalcification Associated With Chronic Kidney Disease
Authors: Erlinda The, Yufeng Zhai, Qingzhou Yao, Lihua Ao, David Fullerton, Xianzhong Meng
Journal: Circulation (2022)

Calcific aortic valve disease (CAVD) is prevalent in the elderly people, particularly those with chronic kidney disease (CKD). Klotho (KL), an anti-aging protein, is expressed mainly in the kidney and the cardiovascular system as soluble and membrane forms. CKD patients have reduced levels of KL and increased levels of fibroblast growth factor 23 (FGF23), a pro-inflammatory mediator that may interact with soluble KL. We have reported that KL reduces the osteogenic response to high phosphate levels, a condition seen in CKD, in human aortic valve interstitial cells (AVICs). This study tested the hypothesis that soluble KL captures FGF23 to prevent aortic valve inflammocalcification induced by CKD. Methods and Results: We developed a novel CKD-CAVD model in old C57 mice (20 months) on AIN-76A diet and treated with adenine and calcitriol. Histology and immunostaining revealed tubular damage and monocyte/macrophage accumulation in kidney tissue of CKD mice. Aortic valve lesions, thickening and calcification, were evident in CKD mice. Serum FGF23 levels were increased while serum KL levels decreased. In addition, KL expression in the aortic valve was reduced. Recombinant FGF23 (0.04 mg/ml) elevated the inflammosteogenic activity in human AVICs. Treatment with recombinant KL (0.5 μg/ml) markedly decreased FGF23-induced inflammosteogenic activation in AVICs. Systemic analysis revealed that FGF23 upregulates YAP/SMAD3 signaling, and inhibition of YAP and SMAD3 reduced the effect of FGF23 on the inflammosteogenic activity in AVICs. In addition, recombinant KL suppressed the activation of this signaling mechanism in AVICs, and treatment of CKD mice with recombinant KL attenuated aortic valve lesions. However, denaturation of KL protein resulted in a loss of its effect on FGF23-induced AVIC inflammosteogenic activation. Further, incubation of FGF23 with recombinant KL not only resulted in the formation of complexes of these two proteins, but also markedly decreased the pro-inflammosteogenic effect of FGF23 in AVICs. Conclusion: This study demonstrates that CKD induces KL insufficiency and FGF23 accumulation that promote aortic valve lesions. Recombinant KL is capable of binding to FGF23 to suppress its pro-inflammosteogenic effect in the aortic valve.
Abstract 13273: Real-World Efficacy of Tafamidis in Patients With Transthyretin Amyloidosis and Heart Failure
Authors: Ahmed Ghoneem, Ammar W Bhatti, Joshua D Mitchell, Jennifer Liu, Kathleen Zhang, Barry Trachtenberg, Ashtoush Wechalekar, Richard Cheng, Suzanne J Baron, Anju Nohria, Daniel Lenihan, Sourbha Dani, Sarju Ganatra
Journal: Circulation (2022)

Background: Tafamidis was associated with reduction in cardiovascular hospitalizations and all-cause mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the ATTR-ACT trial. However, real-world data on the efficacy of tafamidis are limited. Methods: We conducted a retrospective, observational cohort study using the TriNetX research network, a multicenter federated research network with data pooled from electronic health records. Patients with wild-type TTR amyloidosis and heart failure (HF) were identified based on ICD-10 codes on or before May 15, 2021. The study cohort was then divided into two groups based on treatment with tafamidis. Propensity score matching (PSM) was performed to balance the confounders. Rates of heart failure exacerbations (HFE) and all-cause mortality at 12 months were compared between the two cohorts. Results: We identified 1362 patients with wild-type ATTR amyloidosis with HF (tafamidis group =553, non-tafamidis group =809). After PSM, there were 421 patients in each group (mean age: 76 years, Female 14%, White race 64%). During the 12-month follow-up period, 38 (9.0%) patients experienced HFE in the tafamidis group compared to 58 (13.8%) patients in the non-tafamidis group (OR 0.62; CI0.40-0.95, p=0.030). Patients treated with tafamidis had lower all-cause mortality compared to the non-tafamidis group (10.7% vs. 16.4%; OR 0.61, CI 0.40-0.91, p=0.016). The treated cohort had a higher probability of event-free survival for HFE (HR 0.61; 95% CI 0.40-0.92, Log-Rank p= 0.018) and all-cause mortality (HR 0.619; 95% CI 0.425, 0.901, Log-Rank p= 0.011). Conclusion: This real-world analysis confirms that tafamidis use is associated with reduced HF exacerbations and all-cause mortality in patients with wild-type TTR amyloidosis and HF. Longer term follow-up is needed to better understand the utility of tafamadis given the increasing recognition of ATTR-CM and its high cost.
Abstract 13642: Post-Operative Bleeding Risk in TAVR Patients With Atrial Fibrillation
Authors: Mark S Brahier, Shwetha Kochi, Jeffrey Riskin, Ann Kopera, Luke Lawrence, Jay B Patel, Athanasios X Thomaides, Ron Waksman, Lowell Satler, Monvadi B Srichai, Jose D Vargas
Journal: Circulation (2022)

Introduction: Antithrombotic medications are the subject of multiple transcatheter aortic valve replacement (TAVR) randomized control trials. Pragmatically, decisions are complicated by conditions such as atrial fibrillation (AF) that also require lifetime anticoagulation. Our study examines antithrombotic medications in a real-world cohort to identify risk factors for bleeding by 1-year post-TAVR. Methods: This retrospective study includes 844 patients undergoing transfemoral TAVR between 2015 and 2020. Pre- and post-operative medications, comorbidities, and 1-year outcomes were recorded based on review of the medical record. Antithrombotic regiment decisions were made on a case-by-case basis. Bleeding classification followed VARC2 definitions. Patients were stratified into two groups based on history of AF. Multivariable logistic regression was used to determine independent predictors of bleeding. Results: Among the 844 patients, 290 had comorbid AF (34%). Patients with AF were older (80.3 vs 77.8 years; p&lt;0.001), more frequently had cardiovascular comorbidities, and had lower LVEF (52.4% vs 56.8%; p&lt;0.001). Patients with AF were more likely to experience major or life-threatening bleeding (10% vs 5%; p&lt;0.001), but there were no differences in rates of myocardial infarction, cerebrovascular accident, nor death by 1-year follow-up. After controlling for risk factors including anticoagulation and increases to antithrombotic regiment post-operatively, the independent risk predictors of major or life-threatening bleed included female sex [OR 1.522 (1.118-1.741); p=0.018], severe baseline anemia [2.938 (1.146-7.533); p=0.025], and atrial fibrillation [2.195 (1.206-3.997); p=0.010]. Conclusions: Female sex, severe baseline anemia, and comorbid atrial fibrillation are predictors of major or life-threatening bleed by 1 year in patients undergoing transfemoral TAVR, independent of antithrombotic regiment.
Abstract 13753: Higher Social Vulnerability Index is Associated With Increased Mortality Following Cardiac Arrest
Authors: Muchi Ditah Chobufo, Ebad Rahman, Yolande Mbome, Andre Gabriel, Arun Mahtani, Varunsiri Atti, sudarshan balla
Journal: Circulation (2022)

Introduction: Cardiac arrest(CA) is a strong predictor of death. Survival following CA depends on timely initiation of quality cardiopulmonary resuscitation (CPR) and post CA care. The availability of competent individuals, resources and necessary services may be greatly influenced by the characteristics of the communities in which the indexed CA occurs. The Social Vulnerability Index(SVI) is a robust index which reliably ranks counties based on diverse parameters on a scale from 0 to 1. The higher the SVI, the more disadvantaged the community is. Hypothesis: We hypothesize that there is a positive correlation between CA related AAMR( expressed per 100,000 persons) and SVI in the USA. Methods: Using the multiple causes of death database from the Centers for Disease Control and Prevention’s Wide-Ranging Online Data for Epidemiologic Research(1999-2020), we extracted county level deaths with any mention of CA with ICD-10 codes I46.0, I46.1, I46.9. County level SVI was obtained from CDC/ATSDR. SVI was stratified into quintiles. We fitted segmented regression models to evaluate the association between quintiles of SVI scores and CA-related age-adjusted mortality rate (AAMR, expressed per 100,000 persons). Analysis was done using STATA v17 and Joinpoint segmented regression softwares with p-values &lt;0.05 considered statistically significant. Results: The CA related AAMR was 104.5 per 100,000 (95% CI 104.4 - 104.6) for the entire USA, decreasing from 132.9 (132.4 - 133.3) in 1999 to 104.5 (104.2 - 104.8) in 2020. We observed a monotonous increase in AAMR with increasing SVI as shown on figure 1 with an average quintile percentage change of 20.8% (95% CI 13.1 - 29.0) with a p-value of 0.003. Conclusions: Persons who suffer cardiac arrest in counties with higher SVI are more likely to die compared to those who suffer CA in counties with lower SVI. Further research is needed to identify and address the driving factors so as to reduce existing disparity. .
Abstract 14096: Examination of the Serum Metabolome After Dietary Carbohydrate, Milk Protein, and Soy Protein Interventions Identified Novel Metabolites for Blood Pressure: The ProBP Trial
Authors: Changwei Li, Joshua D Bundy, Ling Tian, Ruiyuan Zhang, Jing Chen, Tanika N Kelly, Jiang He
Journal: Circulation (2022)

Introduction: In the Protein and Blood Pressure (ProBP) trial, milk and soy protein supplements reduced blood pressure (BP) compared to carbohydrate intervention. We investigated the underlying mechanisms influencing the effects. Methods: Serum metabolites were profiled at pre-trial baseline and after supplementation with carbohydrate, soy protein, and milk protein, respectively, among 80 ProBP participants. We tested the mediating and modifying effects of metabolites on BP-lowering effects of soy and milk protein interventions. Results: Dietary interventions significantly ( P &lt;6.49х10 -4 ) changed 40 metabolites, of which 29 had reduced levels. Two clusters of metabolites mediated 45.5% and 100% of the effects of soy and milk protein interventions, respectively. Within the clusters, lipid 4-cholesten-3-one had the largest effect and mediated 12.7% ( P =0.03) and 16.3% ( P =0.045) of the effects of soy and milk protein interventions, respectively. At baseline, amino acids 5-oxoproline and taurine, lysophospholipid 1-arachidonoyl-GPA(20:4) , and acylcholines oleoylcholine , dihomo-linolenoyl-choline , and arachidonoylcholine predicted BP increase during carbohydrate intervention; while lipids N-stearoyl-sphinganine(d18:0/18:0) and isoursodeoxycholate and peptide gamma-glutamylserine predicted less reduction of BP during soy protein and milk protein supplements ( P &lt;6.49х10 -4 ). Finally, effects of soy and milk protein interventions on systolic and diastolic BP were influenced by changes of isobutyrylglycine ( P for interaction=0.02 and 9.12х10 -5 , respectively). In the bottom tertile of isobutyrylglycine changes, soy and milk protein reduced 5.10 ( P =0.03) and 4.43 ( P =0.01) mmHg systolic BP and 3.22 ( P =0.03) and 3.12 ( P =0.04) mmHg diastolic BP, respectively; while in the top tertile, the two interventions had no or increasing effects on systolic (β soy protein =-0.04, P =0.98; β milk protein =-2.34, P =0.25) and diastolic BP (β soy protein =3.19, P =0.02; β milk protein =1.08, P =0.43). Conclusions: We documented serum metabolites altered by dietary carbohydrate, milk protein, and soy protein interventions, and identified important metabolites mediating or modifying the BP-lowering effect of milk and soy protein interventions.
Abstract 14105: Stent Ahoy: Ventricular Tachycardia Due to Stent Migration Into the Right Ventricle
Authors: Ali Hasnie, William Fischer, Jayant Khitha
Journal: Circulation (2022)

Case: A 46-year-old female with PMHx of ESRD on dialysis and prothrombin gene mutation presented with acute onset of left breast swelling, redness and pain for nearly 24 hours. She was found to have SVC occlusion and underwent successful SVC recanalization and stent placement with an uncovered 14x40 mm nitinol stent. She presented 4 days later with complaints of chest pain and shortness of breath. Initial vitals were notable for tachypnea with oxygen saturations of nearly 70%, and a blood pressure of 114/71 mmHg. Physical exam demonstrated an obese female in distress. Shortly after arrival in the emergency department, she developed a non-sustained episode of ventricular tachycardia (NSVT). Amiodarone and lidocaine were started, however, she continued to have runs of NSVT. Initial CXR found no acute process but failed to demonstrate the previously placed SVC stent. ECG demonstrated normal sinus rhythm with frequent PVCs and runs of NSVT. A limited echo demonstrated a free edge of an endovascular stent within the right ventricle. TEE demonstrated the stent appeared to be tethered to the septal leaflet of the tricuspid valve with the leading edge free within the right ventricle. Endovascular retrieval was proposed but given the degree of entanglement within the tricuspid leaflets, large stent size, and recurrent NSVT, was deemed an unsuitable therapeutic strategy. Urgent open-heart surgery was performed for removal. The patient tolerated the procedure well and had no further recurrence of NSVT. Discussion: Stent migration is a rare but feared complication of venous stent deployment, with only 32 reported cases over the past 30 years. While NSVT is often attributed to the RVOT, the etiology being the result of migrated stents has been rarely reported. This is the first case to our knowledge of SVC stent migration leading to runs of NSVT. Conclusion: Clinicians must remain cognizant of the risk for venous stent migration and unusual clinical presentations resulting from migration.
Abstract 12773: Computed Tomography Angiography Evaluation of Coronary Plaque Burden in South Asians and Non-Hispanic Whites Over 65 Years of Age
Authors: Venkat S Manubolu, Dhiran Verghese, Luay Alalawi, Jairo Aldana-Bitar, April Kinninger, Tami Crabtree, Hoon J Seok, Shriraj Susarla, Hollin Hamelynck, Katelyn Tan, Sion Roy, James K Min, James Earls, Matthew Budoff
Journal: Circulation (2022)

Introduction: South Asians (SA) have greater atherosclerotic cardiovascular disease (ASCVD) rates than non-Hispanic whites (NHW). SA ethnicity is a risk factor for cardiovascular disease, according to ACC/AHA guidelines. However, data on pattern of atherosclerosis in SA is limited. This study examines plaque burden in SA using quantitative plaque analysis from coronary CT angiography (CCTA). Methods: This is a cross-sectional study comparing the prevalence of atherosclerosis in SA to that of NHW. We identified 104 South Asians who underwent CCTA and quantitative plaque analysis. We then matched 1:1 with 104 non-Hispanic whites. Age, gender, diabetes, hypertension and smoking were utilized to perform a 1: 1 covariate match. Quantification of coronary plaque was conducted using automated plaque analysis software (Cleerly, NY, NY). Percentage atheroma volume (PAV), which is a measure of total plaque divided by total vessel volume, was calculated for each plaque subtypes. Results: A total of 208 subjects formed the study population. The mean age was 71.2±4.9, 66% being male, 38% had DM, 72% reported hypertension, and 10% were past smokers in each group. The SA cohort had significantly higher calcified plaque PAV compared to NHW cohort, median (IQR), 7.6(1.9, 15.5) versus 3.9(1.3, 9.6), (p=0.027). Noncalcified plaque PAV was higher in SA 5.2 (3.0, 7.9) versus 4.5 (2.6,7.2), but not statistically significant (p=0.35). The number of subjects with obstructive disease (&amp;gt50% stenosis) trended higher in the SA cohort (71% of SA versus 60% of NHW) (p=0.08). Conclusions: South Asians had significantly higher calcified plaque PAV and a higher prevalence of obstructive disease compared to the NHW cohort. These results are suggestive of a unique plaque burden and distinctive characteristics in the SA population, which may explain the greater incidence of cardiovascular events and supports the current guidelines.
Abstract 13956: Multidisciplinary Approaches to Treat Ventricular Arrhythmias With Radioablation and Cardiac Sympathectomy (MAVERICS)
Authors: Steven R Scarfone, Emile G Daoud, Toshimasa Okabe, Mahmoud Houmsse, Raul Weiss, Steven J Kalbfleisch, John Hummel, Faisal Matto, Salvatore Savona, Grant Wallace, John Lee, Evan Thomas, Eric Miller, Ahmet Ayan, Michael Weldon, Thura Harfi, Matthew Tong, Whitney Luke, Desmond D'Souza, Jeremy Brownstein, Muhammad Rizwan Afzal
Journal: Circulation (2022)

Background: Ventricular arrhythmias (VAs) are the most lethal arrhythmias. Established therapies to prevent VAs include anti-arrhythmic drugs (AADs) and catheter ablation (CA). For patients with recurrent VAs despite AADs and CA, novel therapies such as cardiac sympathetic denervation (CSD) and stereotactic body radiation therapy (SBRT) exist. This study reports outcomes of CSD and SBRT at a tertiary care academic center. Methods: Study comprises all patients undergoing CSD or SBRT at one center from 10/2018 - 10/2021. Patients with less than 2 months of follow-up were excluded. Retrospective chart review was performed to collate data for demographics, clinical characteristics, arrhythmia burden before and after novel therapies (maximum 12 months), and treatment complications. VA burden in the form of anti-tachycardia pacing (ATP) episodes and defibrillator shocks was assessed as primary efficacy outcome. Treatment complications were assessed as primary safety outcome. Results: Overall, 25 patients underwent novel therapies for VAs, and 13 were excluded for insufficient follow up. Five, 4, and 3 patients underwent CSD, SBRT, and both, respectively. Median age was 66 years (55-72), and 10 (83%) were male. Median left ventricular ejection fraction was 30% (25%-34%). Four patients (33%) had ischemic cardiomyopathy. Median number of AADs and CA prior to novel therapies was 3 (2-5) and 1 (0-2), respectively. Follow up was available for a median of 12 (12-12) months before and 12 (9-12) months after treatment. Overall, VA burden was reduced in 11 of 12 patients (Figure 1). Mean number of ATP and shock episodes was significantly lower after novel therapies (39±43 vs 3±6; p= 0.008). No procedure-related complications were observed. Conclusion: Novel VA treatment modalities are associated with a significantly reduced arrhythmia burden in this single center study. There is a promising role of these therapies as an adjunct to the existing treatment modalities of CA and AADs.
Abstract 13027: Reduced Left Atrial Strain is More Common in Embolic Stroke of Undetermined Source Compared to Non-Cardioembolic Stroke and Can Predict Atrial Fibrillation on Outpatient Cardiac Monitoring
Authors: Zubair Bashir, Edward W Chen, Shuyuan Wang, Eric D Goldstein, Maheen Rana, Liqi Shu, Narendra Kala, Xing Dai, Daniel Mandel, Shadi Yaghi, Phinnara Has, James Simmons, Christopher Song, Philip Haines
Journal: Circulation (2022)

Embolic stroke of undetermined source (ESUS) accounts for 20% of all ischemic strokes with at least 30% having biomarkers of atrial cardiopathy. Traditional parameters of left atrial (LA) structure and function (particularly Left Atrial Volume Index) are similar in ESUS and non-cardioembolic (NCE) stroke subtypes. LA strain measured by speckle tracking echocardiography (STE) is an emerging non-invasive technique to assess LA structure, function, and biomechanics. Our study evaluates whether LA strain differs between patients with ESUS and NCE and whether LA strain magnitude predicts diagnosis of atrial fibrillation (AF) in ESUS. Hospitalized patients with ESUS and NCE stroke subtypes who underwent in-hospital echocardiography were included. STE was performed, and three phases of LA strain (reservoir, conduit, and contractile) were measured. Binary logistic regression analyses were performed to determine the association between different phases of LA strain and stroke subtypes (ESUS vs NCE) as well as AF detection in ESUS patients. A total of 685 patients met the inclusion criteria. Mean age was 65 years; 55% were men; 49% of strokes were NCE; and 51% were ESUS. In patients with ESUS, 57% (189/330) underwent cardiac monitoring. AF was detected in 17.4% (33/189). In fully adjusted binary logistic regression analysis, patients with ESUS had lower LA reservoir strain (adjusted OR 0.99, 95% CI 0.98-0.99, p = 0.039) and LA contractile strain (adjusted OR 0.98, 95% CI 0.97-1.00, p = 0.089). Furthermore, lower LA reservoir strain was associated with AF detection in ESUS patients (OR 0.96, 95% CI 0.93-0.99, p = 0.028). In conclusion, all phases of LA strain were reduced in ESUS compared to NCE. This suggests the presence of atrial cardiopathy in ESUS stroke patients. Furthermore, atrial strain was significantly reduced in ESUS patients found to have AF. These findings may carry mechanistic significance in stroke development and AF detection in ESUS patients.
Abstract 13376: Sleep-Disordered Breathing is Associated With Larger Ventricular Repolarization Instability
Authors: Soroosh Solhjoo, Mark C Haigney, Trishul Siddharthan, Abigail L Koch, Ciprian M Crainiceanu, Naresh M Punjabi
Journal: Circulation (2022)

Introduction: Sleep-disordered breathing (SDB) is a common disorder in the general population that is associated with adverse cardiovascular events, such as sudden cardiac death, but the underlying mechanisms are unclear. Hypothesis: Ventricular repolarization instability is greater in those with severe SDB than those without SDB, independent of other risk factors. Methods: Among the participants of the Sleep Heart Health Study (SHHS), we identified those with SDB who had no diagnosed cardiovascular disease or other factors that could affect cardiac repolarization. Severe SDB was defined as having a respiratory disturbance index (RDI) &gt; 33 events/hour (top 95%ile of the SHHS cohort). We also identified a group of participants matched to the severe SDB group on age, sex, BMI, and race and had RDI &lt; 1.33 events/hour (bottom 25%ile; without SDB). Each group consisted of 61 (45 M and 16 F) participants. Oxygen saturation levels (SpO 2 ) were used to measure hypoxemia burden as the percentage of sleep time with SpO 2 &lt; 90% (T90). Heart rate (HR), heart rate variability (SDNN), and QT variability index (QTVI, a measure of ventricular repolarization instability) were calculated from one-lead ECG recordings. Student’s t- test was used to assess statistical associations. Results: The SDB group had a larger T90 than those without SDB (11.39 ± 1.42% vs 1.32 ± 0.61%, P &lt; 0.001). Participants with SDB also had greater mean HR (P = 0.028), SDNN (P = 0.017), and QTVI (P = 0.027) than those without SDB. Based on a multivariable linear model that included hypoxemia burden, age, BMI, and smoking status, T90 was the only independent predictor of QTVI (P = 0.022). Conclusion: SDB is associated with higher HR, HRV, and QTVI, an indicator of increased instability in ventricular repolarization leading to increased risk for cardiac arrhythmias and sudden cardiac death. The severity of the destabilizing effect of SDB on ventricular repolarization appears to be modified by hypoxemia burden.